Procedural AnxietyPhase 1/2NCT04586504

Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children

A Phase 1/2 study testing Intranasal midazolam in people with Procedural Anxiety, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Dose-finding study to compare intranasal midazolam doses of 0.2, 0.3, 0.4 and 0.5 mg/kg in children undergoing laceration repair to achieve the following aims: Specific Aim #1: To determine the most effective dose of intranasal midazolam for producing adequate sedation state associated with each dose. Read more about this study

Who is it for?: Ages 6 months to 7 years
Conditions the study is for: Procedural Anxiety
What is being tested?: Intranasal midazolam
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 101 participants
Where: 1 siteUnited States
Study dates: 8 Sep 2021to 14 May 2024
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 months to 7 years
All sexes
No healthy volunteers
Child

Who may be able to join

Ages 6 months to 7 years old (i.e. before their 8th birthday)
Simple laceration
Attending physician has decided intranasal midazolam indicated to facilitate repair

Who cannot join

Repair using tissue adhesive (e.g. Dermabond) or staples
Known or confirmed developmental delay
Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)
Autism spectrum disorder
Illness associated with chronic pain
Known allergy to midazolam or any other benzodiazepine

Show all 11Show fewer

Eyelid laceration
Tongue or intraoral lacerations
Nasal obstruction that cannot be easily cleared
Does not speak English or Spanish
Foster children, wards of the state

Trial locations and contacts

1 site in 1 country.

United States1 site

NewYork Presbyterian Morgan Stanley Children's Hospital
New York, New York, 10032

Other trials in United States

About this study

Dose-finding study to compare intranasal midazolam doses of 0.2, 0.3, 0.4 and 0.5 mg/kg in children undergoing laceration repair to achieve the following aims:

Specific Aim #1: To determine the most effective dose of intranasal midazolam for producing adequate sedation state associated with each dose.

Specific Aim #2: To determine the time to recovery and describe the adverse events associated with each dose.

Read the detailed description

Intranasal midazolam is a common and effective sedative whose use in children presenting to emergency departments has been described. However, the doses of intranasal midazolam used have varied greatly, with no identified optimal dose. Doses most commonly described in literature reviews, research studies, and clinical guidelines range from 0.2 to 0.5 mg/kg. There is only one study, retrospective, that compares doses and suggests that clinical efficacy is improved with higher doses, without any clear difference in safety. There is a need for a rigorously-conducted trial to determine the dose of intranasal midazolam that optimizes the adequacy of sedation state without leading to adverse events or compromising emergency department-centric outcomes such as time to onset of sedation and time to recovery. To fill this important and persistent gap in knowledge, the investigator will conduct a dose-finding study using an adaptive trial design to compare intranasal midazolam doses of 0.2, 0.3, 0.4, and 0.5 mg/kg in children undergoing laceration repairs, one of the most common types of minor trauma treated in emergency departments.

Conditions: Procedural Anxiety
Being tested: Intranasal midazolam
Keywords: Intranasal, Midazolam, Pediatric, Laceration repair, Sedation, Anxiolysis, Adaptive trial design, Dose finding

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intranasal midazolamDrug
Also called IN midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.

Study groups in NCT04586504
Study group	Role	What they receive
0.2 mg/kg	Experimental	Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.2 mg/kg. Receives: Drug: Intranasal midazolam
0.3 mg/kg	Experimental	Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.3 mg/kg. Receives: Drug: Intranasal midazolam
0.4 mg/kg	Experimental	Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.4 mg/kg. Receives: Drug: Intranasal midazolam
0.5 mg/kg	Experimental	Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.5 mg/kg. Receives: Drug: Intranasal midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure
The Pediatric Sedation State Scale (PSSS) is scored from 0 to 5, representing a continuum of sedation that spans from over-sedation associated with changes in vital signs (0) to inadequate sedation (5).
Measured: From study drug administration until procedure finished (approximately 60 minutes)

Secondary outcomes (4)

Time to Recovery
Time (in minutes) from procedure completion until a Simplified Aldrete Score (SAS) of at least 6 is achieved. The score ranges from 0 (lowest) to 8 (highest). If a patient already fulfills criteria for recovery at procedure start, then time to recovery is 0.
Measured: From study drug administration until patient discharge (approximately 120 minutes)
Number of Adverse Events
Adverse events will be defined using the Pediatric Emergency Research Canada and Pediatric Emergency Care Applied Research Network Consensus-Based Recommendations. These adverse events include oxygen desaturation; apnea (central, obstructive, laryngospasm); clinically apparent pulmonary aspiration; retching/vomiting; bradycardia; hypotension; excitatory movements; paradoxical response to sedation; unpleasant recovery reactions; and permanent complications (including death).
Measured: From study drug administration until patient discharge (approximately 120 minutes)
Time to Onset of Minimal Sedation
Time (in minutes) from administration of intranasal midazolam until a University of Michigan Sedation State (UMSS) score of 1 is achieved. The UMSS represents a spectrum of depth of sedation ranging from unarousable (4) to awake and alert (0). Note: This outcome was initially listed as a primary outcome, but was changed to a secondary outcome in the IRB-approved protocol and prior to enrollment of the first patient.
Measured: From study drug administration until procedure finished (approximately 60 minutes)
UMSS Scale Score
Depth of sedation will be measured using the University of Michigan Sedation Scale (UMSS). This sedation scale ranges from zero to four with higher numbers indicating deeper sedation.
Measured: From study drug administration until procedure finished (approximately 60 minutes)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Sep 202114 May 2024

First posted14 Oct 2020
Study start8 Sep 2021
Primary completion14 May 2024
Study completion14 May 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Procedural AnxietyStudies of the same condition, open and under way.
More trials run by Columbia UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Sequential selection procedure
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04586504
Sponsor's protocol ID: AAAS7996
Status last verified: Jul 2025
First submitted: 12 Oct 2020
Last updated: 6 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Tsze DS, Ieni M, Fenster DB, Babineau J, Kriger J, Levin B, Dayan PS. Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial. Ann Emerg Med. 2017 May;69(5):600-609. doi: 10.1016/j.annemergmed.2016.08.450. Epub 2016 Nov 4.
PubMed 27823876
Cravero JP, Askins N, Sriswasdi P, Tsze DS, Zurakowski D, Sinnott S. Validation of the Pediatric Sedation State Scale. Pediatrics. 2017 May;139(5):e20162897. doi: 10.1542/peds.2016-2897.
PubMed 28557732
Mellion SA, Bourne D, Brou L, Brent A, Adelgais K, Galinkin J, Wathen J. Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair. J Emerg Med. 2017 Sep;53(3):397-404. doi: 10.1016/j.jemermed.2017.05.029.
PubMed 28992870
Leu C-S, Levin B. On the probability of correct selection in the Levin-Robbins sequential elimination procedure. Stat Sin 1999;9(3):879-91.
Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002 Feb;88(2):241-5. doi: 10.1093/bja/88.2.241.
PubMed 11878656
Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4. doi: 10.1016/j.annemergmed.2008.09.030. Epub 2008 Nov 20.
PubMed 19026467
Elliott CH, Jay SM, Woody P. An observation scale for measuring children's distress during medical procedures. J Pediatr Psychol. 1987 Dec;12(4):543-51. doi: 10.1093/jpepsy/12.4.543. No abstract available.
PubMed 3430286
Tsze DS, Woodward HA, McLaren SH, Leu CS, Venn AMR, Hu NY, Flores-Sanchez PL, Stefan BR, Shen ST, Ekladios MJ, Cravero JP, Dayan PS. Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial. JAMA Pediatr. 2025 Sep 1;179(9):979-986. doi: 10.1001/jamapediatrics.2025.2181.
PubMed 40720114

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Procedural Anxiety trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children
ClinicalTrials.gov ID: NCT04586504
Acronym / sponsor ID: AAAS7996
Conditions: Procedural Anxiety
Keywords: Intranasal, Midazolam, Pediatric, Laceration repair, Sedation, Anxiolysis, Adaptive trial design, Dose finding
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: Columbia UniversityUniversity, hospital or other
Collaborators: Emergency Medicine Foundation, Mailman School of Public Health
Study start: 8 Sep 2021 (actual)
Primary completion: 14 May 2024 (actual)
Study completion: 14 May 2024 (actual)
First posted: 14 Oct 2020 (actual)
Results: Posted 12 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Dose-finding study to compare intranasal midazolam doses of 0.2, 0.3, 0.4 and 0.5 mg/kg in children undergoing laceration repair to achieve the following aims:

Specific Aim #1: To determine the most effective dose of intranasal midazolam for producing adequate sedation state associated with each dose.

Specific Aim #2: To determine the time to recovery and describe the adverse events associated with each dose.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Sequential selection procedure

Arm	Type	Receives
0.2 mg/kg	Experimental	Drug: Intranasal midazolamChildren in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.2 mg/kg.
0.3 mg/kg	Experimental	Drug: Intranasal midazolamChildren in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.3 mg/kg.
0.4 mg/kg	Experimental	Drug: Intranasal midazolamChildren in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.4 mg/kg.
0.5 mg/kg	Experimental	Drug: Intranasal midazolamChildren in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.5 mg/kg.

Who may qualify

Ages: 6 months to 7 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Ages 6 months to 7 years old (i.e. before their 8th birthday)
Simple laceration
Attending physician has decided intranasal midazolam indicated to facilitate repair

Key exclusion criteria (11 listed)

Repair using tissue adhesive (e.g. Dermabond) or staples
Known or confirmed developmental delay
Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)
Autism spectrum disorder
Illness associated with chronic pain

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intranasal midazolamAlso: IN midazolam5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.	Drug	0.2 mg/kg, 0.3 mg/kg, 0.4 mg/kg, 0.5 mg/kg

Primary outcome

Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure
Time frame: From study drug administration until procedure finished (approximately 60 minutes)
The Pediatric Sedation State Scale (PSSS) is scored from 0 to 5, representing a continuum of sedation that spans from over-sedation associated with changes in vital signs (0) to inadequate sedation (5).

4 secondary outcomes

Time to Recovery
Time frame: From study drug administration until patient discharge (approximately 120 minutes)
Number of Adverse Events
Time frame: From study drug administration until patient discharge (approximately 120 minutes)
Time to Onset of Minimal Sedation
Time frame: From study drug administration until procedure finished (approximately 60 minutes)
UMSS Scale Score
Time frame: From study drug administration until procedure finished (approximately 60 minutes)

Results and safety

Results posted to the registry on 12 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.2 mg/kg	19	19
0.3 mg/kg	24	24
0.4 mg/kg	29	29
0.5 mg/kg	29	29

Primary outcome: Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure

Time frame: From study drug administration until procedure finished (approximately 60 minutes). Count of participants. Unit: Participants

Measure	0.2 mg/kg n = 19	0.3 mg/kg n = 24	0.4 mg/kg n = 29	0.5 mg/kg n = 29
Value	9	12	20	19

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From time of intranasal midazolam administration until discharge from emergency department (approximately 120 minutes). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.2 mg/kg	0 of 19 (0%)	0 of 19 (0%)	0 of 19
0.3 mg/kg	0 of 24 (0%)	0 of 24 (0%)	0 of 24
0.4 mg/kg	0 of 29 (0%)	2 of 29 (6.9%)	0 of 29
0.5 mg/kg	0 of 29 (0%)	0 of 29 (0%)	0 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27823876Tsze DS, Ieni M, Fenster DB, Babineau J, Kriger J, Levin B, Dayan PS. Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial. Ann Emerg Med. 2017 May;69(5):600-609. doi: 10.1016/j.annemergmed.2016.08.450. Epub 2016 Nov 4.
Background: PubMed 28557732Cravero JP, Askins N, Sriswasdi P, Tsze DS, Zurakowski D, Sinnott S. Validation of the Pediatric Sedation State Scale. Pediatrics. 2017 May;139(5):e20162897. doi: 10.1542/peds.2016-2897.
Background: PubMed 28992870Mellion SA, Bourne D, Brou L, Brent A, Adelgais K, Galinkin J, Wathen J. Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair. J Emerg Med. 2017 Sep;53(3):397-404. doi: 10.1016/j.jemermed.2017.05.029.
BackgroundLeu C-S, Levin B. On the probability of correct selection in the Levin-Robbins sequential elimination procedure. Stat Sin 1999;9(3):879-91.
Background: PubMed 11878656Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002 Feb;88(2):241-5. doi: 10.1093/bja/88.2.241.
Background: PubMed 19026467Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4. doi: 10.1016/j.annemergmed.2008.09.030. Epub 2008 Nov 20.
Background: PubMed 3430286Elliott CH, Jay SM, Woody P. An observation scale for measuring children's distress during medical procedures. J Pediatr Psychol. 1987 Dec;12(4):543-51. doi: 10.1093/jpepsy/12.4.543. No abstract available.
Results publication: PubMed 40720114Tsze DS, Woodward HA, McLaren SH, Leu CS, Venn AMR, Hu NY, Flores-Sanchez PL, Stefan BR, Shen ST, Ekladios MJ, Cravero JP, Dayan PS. Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial. JAMA Pediatr. 2025 Sep 1;179(9):979-986. doi: 10.1001/jamapediatrics.2025.2181.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniel S. Tsze, MD, MPH principal investigator

Columbia University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intranasal midazolam in people with Procedural Anxiety, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure (time frame: From study drug administration until procedure finished (approximately 60 minutes)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04586504, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.